IFNγ induces JAK1/STAT1/p65 NFκB-dependent interleukin-8 expression in ovarian cancer cells, resulting in their increased migration.
Cell invasion
Interferon-γ
Interleukin-8
JAK1
Ovarian cancer
STAT1
p65 NFκB
Journal
The international journal of biochemistry & cell biology
ISSN: 1878-5875
Titre abrégé: Int J Biochem Cell Biol
Pays: Netherlands
ID NLM: 9508482
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
25
06
2021
revised:
20
09
2021
accepted:
04
10
2021
pubmed:
10
10
2021
medline:
17
12
2021
entrez:
9
10
2021
Statut:
ppublish
Résumé
Interferon-γ (IFNγ) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFNγ has been used in cancer treatment. However, IFNγ also has tumor-promoting functions that are less well understood. Here, we show that IFNγ induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFNγ-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NFκB, and is associated with an increased occupancy of K314/315 acetylated p65 NFκB and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody reduces IFNγ-induced migration of OC cells, and their invasion ability in 3D spheroids. Together, these findings identify IL-8 as a novel target induced by IFNγ/JAK1/STAT1/p65 NFκB signaling, and indicate that the IFNγ-induced IL-8 contributes to IFNγ pro-tumorigenic effects in ovarian cancer cells.
Identifiants
pubmed: 34626802
pii: S1357-2725(21)00174-6
doi: 10.1016/j.biocel.2021.106093
pmc: PMC8639749
mid: NIHMS1747629
pii:
doi:
Substances chimiques
CXCL8 protein, human
0
Interleukin-8
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
106093Subventions
Organisme : NCI NIH HHS
ID : R15 CA202775
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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